Publication: Metastatik meme kanseri tedavisinde NF-κB sinyal yolağı regülatörlerinin araştırılması
Abstract
Amaç: BCL3 geni, NF-κB sinyal yolağı hedef genlerinin transkripsiyon aktivasyonunun düzenlenmesinde kritik bir rol oynayan ve metastaz gibi çeşitli hücresel süreçleri düzenlemek için spesifik moleküllerle etkileşime giren, bir proto-onkogen adayıdır. Bu çalışmada, metastatik meme kanserinde BCL3’ün, etkileşen partnerlerinin (NFKB1, NFKB2) ve diğer BCL3 etkileşimli genlerin (CYLD, GSK3B, CCND1, TP53, CDH2, SMAD3, TGFB1) ekspresyon profilinin metastaz ile ilişkisini araştırmayı amaçladık.Gereç ve yöntem: mRNA ekspresyon seviyeleri, metastatik meme kanseri hastalarında (n = 55) ve sağlıklı kontrol donörlerinde (n = 50) qRT-PCR ile değerlendirildi. İstatistiksel analiz için SPSS 26 ve Graph Prism programları kullanıldı. Fark, p <0.05'te istatistiksel olarak anlamlı kabul edildi. Bulgular: BCL3 mRNA ekspresyon seviyeleri, sağlıklı kontrol grubuna kıyasla metastatik meme kanserli hastalarda aşağı regüle edildiği bulundu (p=0.0004). Metastatik meme hastalarında sağlıklı kontrollere göre NFKB1 (p=0.0005), NFKB2 (p=0.0001), CYLD (p=0.00042) ve TP53 (p=0.0287) ekspresyon düzeyleri anlamlı olarak daha düşüktü. CCND1 ve CDH2 gen ekspresyonları metastatik grupta önemli ölçüde yukarı regüle edildiği tespit edildi (sırasıyla p=0.0009 ve p=0.0030). GSK3B, SMAD3 ve TGFB1 ekspresyonları gruplar arasında önemli ölçüde farklılık göstermedi. Sonuç: Bu çalışmada, BCL3'ün birden fazla metastatik lokasyonu olan metastatik meme kanseri hastalarında ilk kez çelişkili rollerini sunduk. NF-κB regülatörlerinin aşağı regüle edilmiş ekspresyonu, BCL3 geni ve NFKB1, NFKB2'nin metastatik durumun erken tespiti için önemli bir klinik biyobelirteç görevi sunabilir.
Objective: BCL3 is a candidate proto-oncogene that plays a critical role in the regulation of transcription activation of NF-κB signaling pathway target genes and interacts with specific molecules to regulate various cellular processes such as metastasis. In the present study, we aimed to investigate the correlation of expression profile of BCL3, its interacting partners (NFKB1, NFKB2), and other BCL3 interacting genes (CYLD, GSK3B, CCND1, TP53, CDH2, SMAD3, TGFB1) with metastatic breast cancer.Material and methods: mRNA expression levels were evaluated in metastatic breast cancer patients (n=55) and in healthy control donors (n=50) by RT‑qPCR. SPSS 26 and Graph Prism programs were used for statistical analysis. Difference was considered statistical significant at p< 0.05. Results: Expression levels of BCL3 mRNA was downregulated in metastatic breast cancers patients compared to healthy control group (p= 0.0004). Subsequently, expression levels of the NFKB1 (p= 0.0005), NFKB2 (p= 0.0001), CYLD (p= 0.00042) and TP53 (p= 0.0287) were significantly lower in metastatic breast patients compared to healthy controls. CCND1 and CDH2 gene expressions were significantly upregulated in metastatic group (p= 0.0009; and p= 0.0030, respectively). GSK3B, SMAD3 and TGFB1 expressions were not significantly different between groups.Conclusion: In this study we presented contradictory roles of BCL3 in metastatic breast cancer patients with multiple metastatic locations for the first time. Downregulated expression of NF-κB regulators suggest that BCL3 gene and NFKB1, NFKB2 might act as a biomarker for metastasis.
Objective: BCL3 is a candidate proto-oncogene that plays a critical role in the regulation of transcription activation of NF-κB signaling pathway target genes and interacts with specific molecules to regulate various cellular processes such as metastasis. In the present study, we aimed to investigate the correlation of expression profile of BCL3, its interacting partners (NFKB1, NFKB2), and other BCL3 interacting genes (CYLD, GSK3B, CCND1, TP53, CDH2, SMAD3, TGFB1) with metastatic breast cancer.Material and methods: mRNA expression levels were evaluated in metastatic breast cancer patients (n=55) and in healthy control donors (n=50) by RT‑qPCR. SPSS 26 and Graph Prism programs were used for statistical analysis. Difference was considered statistical significant at p< 0.05. Results: Expression levels of BCL3 mRNA was downregulated in metastatic breast cancers patients compared to healthy control group (p= 0.0004). Subsequently, expression levels of the NFKB1 (p= 0.0005), NFKB2 (p= 0.0001), CYLD (p= 0.00042) and TP53 (p= 0.0287) were significantly lower in metastatic breast patients compared to healthy controls. CCND1 and CDH2 gene expressions were significantly upregulated in metastatic group (p= 0.0009; and p= 0.0030, respectively). GSK3B, SMAD3 and TGFB1 expressions were not significantly different between groups.Conclusion: In this study we presented contradictory roles of BCL3 in metastatic breast cancer patients with multiple metastatic locations for the first time. Downregulated expression of NF-κB regulators suggest that BCL3 gene and NFKB1, NFKB2 might act as a biomarker for metastasis.